NUTREASE POWDER - NATURE’S BLEND OF PROTEIN, FIBER, MULTIVITAMIN, MULTIMINERAL & ANTIOXIDANT SUPPORT IMPROVES THE EFFECTIVENESS OF THE ANTITUBERCULOSIS DRUGS

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16 | P a g e ISSN (Online): 2581-5059 Website: www.mjbas.com

NUTREASE POWDER - Nature’s Blend of Protein, Fiber, Multivitamin,

Multimineral & Antioxidant Support Improves the Effectiveness of the

Antituberculosis Drugs

Govind Shukla, Monica Yadav, Madugula Mahender & C.J.Sampath Kumar

Lactonova Nutripharm (P) Ltd, Makers of NUTREASE Powder, 81/3, IDA Mallapur, Hyderabad, Telangana, India-500 076.

Article Received: 03 October 2019 Article Accepted: 17 January 2020 Article Published: 05 February 2020

INTRODUCTION

Malnutrition and tuberculosis are both problems of considerable magnitude in most of the underdeveloped regions

of the world. It is important to consider, how these two problems tend to interact with each other.

The term consumption has been virtually synonymous with tuberculosis throughout the history.1 and the link

between tuberculosis and malnutrition has long been recognized; malnutrition may predispose people to the

development of clinical disease and tuberculosis can contribute to malnutrition. 2

Before the advent of antituberculosis chemotherapy, a diet rich in calories, proteins, fats, minerals, and vitamins

was generally considered to be an important, if not essential factor in treatment of tuberculosis. The introduction of

specific antituberculosis drugs, however, has so radically altered the management of the disease that the role of diet

should be considered in the light of the advances in treatment.

In the 21st century, tuberculosis is still the most frequent underlying cause of wasting worldwide. However,

pathophysiology of wasting in tuberculosis remains poorly understood.3 The prevalence of widespread

malnutrition in the population may be expected to pose some special problems with regard to the control of the

tuberculosis in the developing countries from the larger point of view of prevention and therapeutic management of

individual cases, from the narrower clinical point of view.

The direct evidence of effect of nutrition on tuberculosis is difficult because of whole complex of coincident

environmental factors. Despite these limitations, the weight of evidence still favors the view that malnutrition may

be an important factor in the high mortality and morbidity from tuberculosis in population subjected to food

shortage.4 In any consideration of the role of nutrition in tuberculosis, three important questions arise.4

A B S T R A C T

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High prevalence of human immunodeficiency (HIV) infection in the underdeveloped countries further aggravates

the problem of malnutrition and tuberculosis. HIV infection is an important risk factor for development of

tuberculosis and adversely affects the nutritional status of patient.

EFFECTS OF MALNUTRITION ON TUBERCULOSIS

There are several experimental, clinical, and epidemiological studies demonstrating the effects of malnutrition on

tuberculosis.

Epidemiological studies

It has been pointed out that tuberculosis mortality rates in different economic groups in a community tend to vary

inversely with their economic levels. There are also numerous observations pointing to increase in tuberculosis

mortality in various countries during times of war and famine.5

There are numerous studies dealing with the effects of different diets on tuberculosis patients, and widely divergent

and contradictory claims have been made. Difficulty in interpretation of these studies is influence of other factors

on infection. Among tuberculin skin test positive U.S. navy recruits, the risk of tuberculosis was nearly four-fold

higher among men who were at least 10% underweight at baseline than in men who were at least 10%

overweight.6 In a study among 1,717,655 Norwegians, >15-years old who were followed for 8–19 years after

intake into a radiographic screening program, the relative risk of tuberculosis among persons in the lowest body

mass index (BMI) category was more than five-fold higher than the group in the highest BMI category, and it was

independent of sex, age, and radiographic findings.7

In another study conducted in London, it was found that Hindu Asians had an increased risk of tuberculosis

compared with Muslims. Religion had no independent influence after adjustment for vegetarianism (common

among Hindu Asians).8 There was a trend of increasing risk of tuberculosis with decreasing frequency of meat or

fish consumption. Lacto-vegetarians had an 8.5-fold risk compared with daily meat/fish eaters. Decreased

immunocompetence associated with a vegetarian diet may result in increased mycobacterial reactivation.

Poor nutrition among patients who have undergone gastrectomy may be a risk factor for the reactivation of

tuberculosis. There are other studies indicating that incidence of tuberculosis is unusually high among

malnourished people.9

Now it is important to consider how malnutrition can increase risk of tuberculosis. The host protective immune

mechanism of infection with Mycobacterium tuberculosis depends critically on the interaction and cooperation

between monocyte-macrophages and T-lymphocytes and their cytokines.10 Substantial experimental evidence

suggests that malnutrition can lead to secondary immunodeficiency that increases the host's susceptibility to

infection. Increased risk of tuberculosis can result from alteration in the individual protective function of, or the

interaction between T-lymphocytes and macrophages because of nutritional insult.11 The reactivation of latent or

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malnutrition has been identified as an important risk factor for the predisposition to intracellular infection leading

to death.13

Animal studies

Though there are several studies on experimental animals that have concluded contributory role of malnutrition on

tuberculosis, an important snag in the interpretation of experimental data is the question as to how far these data

obtained in the experimental animals are really applicable to human subjects. The natural history and evolution of

tuberculosis in the animals and human beings need not necessarily be the same, and of course, the nutritional

requirements of the animals and human subjects are also different.5

It was reported that protein calorie malnutrition markedly enhanced bacterial growth and dissemination in mice

resulting in rapidly fatal tuberculosis infection and a markedly elevated bacillary load in the lungs of protein

deficient mice.11

Study on guinea pigs demonstrated that protein malnutrition impairs the protective interaction between

macrophages and T-lymphocytes and/or the acquisition of mycobactericidal and mycobacteriostatic activity by

macrophages in the presence of adequate activation signals. 14

Protein deficiency prevented guinea pigs from generating a population of antigen-specific-immune lymphocytes

and/or impaired the proliferation capacity of these cells.15

Cytokines play a central role in mediating antimycobacterial immunity. Interleukin-2 (IL-2) is required to initiate

and amplify immune responses. IL-2 production was depressed in chronic protein deficient guinea pigs vaccinated

with M bovis BCG.16

Result of a study on guinea pigs demonstrated that protein malnutrition potentiates the M.

tuberculosis H37Rv-infected macrophages-monocytes to produce higher levels of transforming growth factor-β

(TGF-β) which is a likely mediator of immunosuppression and immunopathogenesis in tuberculosis.14

In nutshell, it can be said that malnutrition exerts detrimental effects on many aspects of host immune responses

against mycobacterial infection. First, dietary deficiency causes thymic atrophy and impairs the generation and

maturation of T-lymphocytes in animal models of tuberculosis, resulting in reduced number of immunocompetent

T-cells in lymphoid compartments including the blood.

Second, deficiency of protein and other nutrients impair T-cell functions, including decreased production of Th1CK

IL-2 and IFN-γ and depressed tuberculin reaction and PPD-induced lymphoproliferation in guinea pigs and mice

infected with virulent M. tuberculosis.

Third, protein malnutrition impairs sequestration or trapping of reactive T-lymphocytes and loss of tuberculosis

resistance following BCG vaccination. Finally, protein malnutrition potentiates M tuberculosis H37Rv infected

monocytes-macrophages to produce higher level of TGF-β-a cytokine which has been implicated as a likely

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19 | P a g e ISSN (Online): 2581-5059 Website: www.mjbas.com EFFECTS OF TUBERCULOSIS ON NUTRITIONAL STATUS

Nutritional status is significantly lower in patients with active pulmonary tuberculosis compared with healthy

controls in different studies in Indonesia, England, India, and Japan.17

Tuberculosis patients have been found to have lower serum albumin concentration than controls. 17Tuberculosis is

probably associated with more severe malnutrition than other chronic illnesses; in an Indian study, the nutritional

status of patients with tuberculosis was worse than that of those with leprosy. A study in Uganda demonstrated that

poor nutritional status is common among adults with pulmonary tuberculosis. 18 In yet another Indian study,

tuberculosis patients were respectively 11 and 7 times more likely to have a BMI < 18.5 and mid-arm

circumference < 24 cm. 19

For any infection, there is a complex interaction between the host response and the virulence of the organisms,

which modulates the overall metabolic response and the degree and the pattern of tissue loss. In patients with

tuberculosis, a reduction in appetite, nutrient malabsorption, micronutrient malabsorption, and altered metabolism

leads to wasting.20,21

In a study, Indian patients with pulmonary tuberculosis were compared with malnourished and normally nourished

healthy subjects. Whereas protein synthesis and breakdown in the fasting state were not significantly different

between groups, patients with tuberculosis used a larger proportion of proteins from oral feeding for oxidation and

hence for energy production than did either control group. Such failure to channel food protein into endogenous protein synthesis has been termed “Anabolic block”. This anabolic block represents one of the mechanisms for

wasting in tuberculosis and other inflammatory status.21,22

Anorexia is also a contributing factor for wasting in tuberculosis. In an unselected U.S. cohort of patients diagnosed

with tuberculosis, 45% lost weight and 20% had anorexia. 23 Increased production of cytokines with lipolytic and

proteolytic activity cause increased energy expenditure in tuberculosis. 24 Leptin may also play an important role

in wasting. 25In a study, malnutrition has been associated with atypical presentations of tuberculosis.26

Role of micronutrients

Because of diverse metabolic characteristics and functions, micronutrients have presently been accepted as

essential for optimum human health. Micronutrients deficiency is considered to be the most frequent cause of

secondary immunodeficiency and infection related morbidity including tuberculosis.

Zinc

Zinc deficiency affects the host defenses in a variety of ways. It results in decreased phagocytosis and leads to a

reduced number of circulating T-cells and reduced tuberculin reactivity, at least in animals.17 In vitro cellular

killing by macrophages was found to be reduced during zinc deficiency and rapidly restored after zinc

supplementation.27

Various studies on patients with tuberculosis had shown significantly lower plasma zinc level than those without

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of antituberculosis therapy (ATT). Thus, it may be suggested that plasma zinc status is likely a marker for

monitoring the severity of disease and response to therapy. 17,28,29

Zinc deficiency in tuberculosis is likely due to redistribution of zinc from plasma to other tissues or reduction of the hepatic production of the zinc carrier protein α2-macroglobulin and to a rise in the production of metallothionein, a

protein that transports zinc to the liver.17

Reduction in plasma zinc concentration was shown in tuberculosis patients after two months of treatment. This

phenomenon may be because during the intensive phase of ATT, the antituberculosis drugs were used to kill the

population of replicating bacilli and zinc may play important role in the macrophage contribution to host defenses

at the site of infection. 30

The other possible mechanisms could be the effect of antituberculosis drugs on zinc absorption. Ethambutol was

shown in rats to increase not only zinc absorption but also urinary zinc losses, resulting in reduced circulating zinc

concentration.31

Zinc supplementation of patients with pulmonary tuberculosis and bacterial pneumonia was shown to increase

immune function. 32

In a study, it was found that PPD indurations were larger in children receiving zinc and zinc increases the PPD

induration size in children irrespective of nutritional status.33

Zinc has essential role in vitamin A metabolism. Studies in humans and animals have shown that zinc deficiency

impairs the synthesis of retinal binding proteins and reduces plasma retinal concentration. 34 Therefore, it appears

that zinc supplementation has a beneficial effect on vitamin A metabolism which has important role in tuberculosis.

An adequate supply of zinc may also limit free radical membrane damage during inflammation.35

Vitamin A

It has been shown that vitamin A has immune competent role in human tuberculosis. Vitamin A was reported to

inhibit multiplication of virulent bacilli in cultured human macrophages.36 In addition, vitamin A has a vital role in

lymphocyte proliferation and in maintaining the function of epithelial tissues. 37 Vitamin A is essential for normal

functioning of T and B lymphocytes, macrophage activity, and generation of antibody response.38

A study from Rwanda reported vitamin A deficiency among adults with tuberculosis. Concentration of vitamin A

was found to be lower in tuberculosis patients than that in controls in many studies. 39,40 The low concentration of

retinal in plasma can be due to number of factors including reduced intake or reduced absorption of fat.

Additionally, infection itself can compromise vitamin A status in number of ways. 41 Vitamin A is excreted in the

urine in patients with fever and this has been confirmed in subjects with acute infection including

pneumonia.42 During the acute phase response, leakage of proalbumin through the vascular endothelium occurs;

and production of retinal binding proteins and prealbumin by liver is reduced. 41In addition, requirement of

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vitamin A levels observed in tuberculosis patients returned to normal at the end of ATT without vitamin A

supplementation.43Vitamin A deficiency increases bacterial adherence to respiratory epithelial cells.44

In the prechemotherapeutic era, cod liver oil rich in vitamin A and D was used regularly to strengthen host

defence. 45 Supplementation of vitamin A appears to increase survival among chicks infected with M.

tuberculosis and enhances both T-lymphocyte and antibody responses to M. tuberculosis.46

Vitamin D

Vitamin D plays a role in the function of macrophages, key factor in host resistance in tuberculosis. Abnormalities

in vitamin D status have been reported in tuberculosis. Genetic variations in the vitamin D receptor were identified

as a major determinant of the risk for tuberculosis in Africans.47

Vitamin D deficiency itself was shown to be a risk factor for tuberculosis. 48Adults with untreated tuberculosis in

Indonesia were shown to have significantly lower 25-hydroxy-vitamin D compared with controls.49

Studies have yielded inconsistent findings regarding serum or plasma calcium concentration during tuberculosis. A

study in Africa has related hypocalcemia to moderate to extensive radiographic disease.50

Vitamin E

In many studies, concentration of vitamin E was found to be significantly lower in tuberculosis patients than

healthy controls.39,51

Vitamin C

Studies have linked vitamin C deficiency with tuberculosis.39,51 concentrations of antioxidant vitamin C, vitamin

E, and vitamin A were significantly lower in tuberculosis patients and high malonaldehyde concentration was

associated with clinical severity.52

Selenium

The essential trace element selenium has an important function in maintaining the immune processes and thus may

have a critical role in clearance of mycobacteria. Selenium has been found as significant factor in the relative risk

for developing mycobacterial diseases in HIV positive patients. 53

A recent Indian study measured concentrations of circulating antioxidants and markers of oxidative stress in

tuberculosis patients. Results showed lower antioxidant potential (lower levels of superoxide dismutase, catalase,

glutathione, and ascorbic acid) and enhanced lipid peroxidation products (malonaldehyde) in tuberculosis patients.

Antioxidant potential increased with treatment.54

Iron

Anemia is highly prevalent among adults with pulmonary tuberculosis.17 In a study conducted in Ghana, 50%

adults with pulmonary tuberculosis had significantly lower hemoglobin than healthy matched controls. Iron

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In a study, concentration of hemoglobin was lower in tuberculosis patients than that in controls17and those of zinc

protoporphyrin (ZPP) were significantly higher than in controls. Elevated concentration of ZPP, a measure of free

erythrocyte porphyrin, is indicative of iron deficient erythropoiesis.56

There are two explanations for the association of low iron status and infection. One is that anemia results from

chronic infection and the other is that iron deficiency would increase susceptibility to infection such as tuberculosis.

17

Copper

In a recent study, compared with the control group, the concentrations of iron, zinc, and selenium were significantly

lower while that of copper and copper/zinc ratio were significantly higher in the serum of tuberculosis

patients.57 The serum concentration of zinc increased and serum copper concentration and copper/zinc ratio

decreased significantly after antituberculosis chemotherapy.

Polyunsaturated fatty acids

In a study, eicosanoid synthesis was studied in macrophages of guinea pigs fed with different amounts of omega-6

fatty acids and omega-3 fatty acids. It was concluded that supplementing the diet with (n-3-) fatty acids can affect

resistance to M. tuberculosis, whereas supplementing with (n-6-) fatty acids does not.58

Cholesterol

Hypocholesterolemia is common among tuberculosis patients and is associated with mortality in miliary

tuberculosis cases. In vitro studies concluded that cholesterol-rich diet accelerated the sterilization rate of sputum

culture in pulmonary tuberculosis patients suggesting that cholesterol should be used as a complementary measure

in ATT.59

MECHANISM OF ACTION OF NUTREASE POWDER

Nutrease contains standardized plant-based vitamins and minerals which include a diverse mixture of substances

including dozens of closely related vitamers and phytonutrients to help potentiate insulin action and thus influence

carbohydrate, lipid and protein metabolism. Targeted botanicals and antioxidants like curcuminoids,

sulforaphaneglucosinolate from Broccoli Extract and Ginger Extract to help regulate metabolism, stimulate

digestion and to provide long-lasting cell protection from free radical damage. Probiotics and prebiotics like

Lactobacillus gasseri and Inulin to help balance intestinal flora, reduce waist circumference and reduce adipocyte

size through inhibition of leptin levels. Good fats like omega 3,6& 9 from Flaxseed and Medium Chain

Triglycerides (MCT), help to maintains healthy levels of blood sugar and triglycerides, enhance metabolism to

burn more calories. Optimum fibers like alpha cyclodextrins, partially hydrolyzed guar gum, and oat fiber to help

promote intestinal regularity, to increase the satiety and improve glycemic effect of meal. Plant enzymes like

bromelain and papain for better digestion and absorption of proteins. Premium blend of protein concentrate and pea

protein isolate to meet the daily protein requirements and to maintain lean muscle mass. Added with natural

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COMPOSITION OF NUTREASE POWDER _{PHARMACOLOGICAL ACTION OF}

EACHINGREDIENTS OF NUTREASE

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30 | P a g e ISSN (Online): 2581-5059 Website: www.mjbas.com SUPPLEMENT FACTS

Presentation:POWDER

Usage: As a food supplement. It is a combination of Natural vitamins and minerals Natural Antioxidant

Phyto-Nutrients to improve health and vitality. Provides Natural Antioxidant support to improve the effectiveness

of the antituberculosis drugs.

Contra-indications:Product is contra-indicated in persons with Known hypersensitivity to any component of the

product hypersensitivity to any component of the product.

Recommended usage:Once or twice a day along with portion controlled nutritious meals and exercise.

One Serving (30g- 1 Scoop) provides 104 Calories, 11.61g of proteins, 6.64g of Fiber and 1.82g of Sugar per day.

“Do not exceed the recommended daily dose”.

Directions for Use:Take one level scoop (30g) with skimmed milk or water to make a cup of 200ml. Gently shake

well in shaker or stir well until the powder is evenly dispersed and drink immediately.

Administration:Taken by oral route at any time with food.

Precautions: Food Supplements must not be used as a substitute for a varied and balanced diet and a healthy

lifestyle. This Product is not intended to diagnose, treat, cure or prevent any diseases. Do not exceed the

recommended daily dose.

Warnings: If you are taking any prescribed medication or has any medical conditions always consults doctor or

healthcare practitioner before taking this supplement.

Side Effects:Mild side effects like nausea, headache and vomiting in some individuals have been reported.

Storage:Store in a cool, dry and dark place.

SUMMARY & CONCLUSION

Nutritional supplementation may help to improve outcome in tuberculosis patients. A study found that nutritional

counseling to increase energy intake combined with provision of supplements, when started during the initial phase

of tuberculosis treatment, produced a significant increase in body weight, total lean mass, and physical function

after six weeks. A large proportion (46%) of the early weight gain comprised lean tissue, confirming the findings

that tuberculosis can mount a protein anabolic response on feeding.

Nutritional supplementation may represent a novel approach for fast recovery in tuberculosis patients. In addition,

raising nutritional status may prove to be an effective measure to control tuberculosis.

Nutrease Powder, A blend of natural Antioxidant Phytonutrients to prevent & cure diseases. Antioxidant

phytochemicals found in Nutrease powder plays an important role in the prevention and treatment of tuberculosis.

They often possess strong antioxidant and free radical scavenging abilities, which are also the basis of other

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modulating immune function to prevent specific diseases. Being natural products, they hold a great promise in

clinical therapy to improve the effectiveness of the antituberculosis drugs.

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56. Hastka J, Lesserre JJ, Schwarzbeck A, Strauch M, Hehlmann R. Washing erythrocytes to remove interferents in

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